Role of dual-specificity protein phosphatase-5 in modulating the myogenic response in rat cerebral arteries
Role of dual-specificity protein phosphatase-5 in modulating the myogenic response in rat cerebral arteries
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DOI：
10.1152/japplphysiol.01026.2011
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Harder, David R.
中科院分区：
文献类型：
--
作者：
Wickramasekera, Nadi T.;Gebremedhin, Debebe;Harder, David R.
双特异性蛋白磷酸酶-5在调节大鼠脑动脉肌生成反应中的作用。中国生物医学工程学报（英文版），2014,31(2):444 - 444。首次发表于2012年11月21日；doi: 10.1152 / japplphysiol.01026.2011。本研究探讨了双特异性蛋白磷酸酶-5 （DUSP-5）在器官培养脑动脉段压力诱导的肌生成反应中的作用。在这些研究中，我们首先比较了新鲜分离和器官培养的脑动脉段对血管内压力、血管舒张剂和血管收缩剂刺激、大电导动脉Ca2+活化K+ (K- ca)单通道电流的活性和DUSP-5酶稳定蛋白表达的反应。结果表明，在器官培养的脑动脉段中，维持压力依赖性肌源性血管收缩，DUSP-5蛋白表达，内皮依赖性和非依赖性扩张，激动剂诱导的收缩，以及与新鲜分离的脑动脉相似的单一K-Ca通道传导。此外，通过器官培养脑动脉段的渗透转染技术，基因特异性小干扰RNA （siRNA）诱导DUSP-5 mRNA和蛋白的敲低，这与压力依赖性脑动脉肌原性收缩增强和pkc - β II磷酸化增加有关。此外，siRNA敲低DUSP-5降低了磷酸化ROCK和ERK1的水平，而磷酸化ERK2的水平没有变化。ERK1/2磷酸化的药理抑制可显著减轻压力诱导的脑动脉肌原性收缩。本研究的发现表明，DUSP-5，固有于脑动脉肌肉细胞，似乎调节压力依赖性肌源性脑动脉收缩的信号传导，这对于维持持续的脑血流量至关重要。
Role of dual-specificity protein phosphatase-5 in modulating the myogenic response in rat cerebral arteries. J Appl Physiol 114: 252-261, 2013. First published November 21, 2012; doi:10.1152/japplphysiol.01026.2011.-The present study examined the role of the dual-specificity protein phosphatase-5 (DUSP-5) in the pressure-induced myogenic responses of organ-cultured cerebral arterial segments. In these studies, we initially compared freshly isolated and organ-cultured cerebral arterial segments with respect to responses to step increases in intravascular pressure, vasodilator and vasoconstrictor stimuli, activities of the large-conductance arterial Ca2+-activated K+ (K-Ca) single-channel current, and stable protein expression of DUSP-5 enzyme. The results demonstrate maintained pressure-dependent myogenic vasoconstriction, DUSP-5 protein expression, endothelium-dependent and -independent dilations, agonist-induced constriction, and unitary K-Ca channel conductance in organ-cultured cerebral arterial segments similar to that in freshly isolated cerebral arteries. Furthermore, using a permeabilization transfection technique in organ-cultured cerebral arterial segments, gene-specific small interfering RNA (siRNA) induced knockdown of DUSP-5 mRNA and protein, which were associated with enhanced pressure-dependent cerebral arterial myogenic constriction and increased phosphorylation of PKC-beta II. In addition, siRNA knockdown of DUSP-5 reduced levels of phosphorylated ROCK and ERK1 with no change in the level of phosphorylated ERK2. Pharmacological inhibition of ERK1/2 phosphorylation significantly attenuated pressure-induced myogenic constriction in cerebral arteries. The findings within the present studies illustrate that DUSP-5, native in cerebral arterial muscle cells, appears to regulate signaling of pressure-dependent myogenic cerebral arterial constriction, which is crucial for the maintenance of constant cerebral blood flow to the brain.